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Urotensin-II system in genetic control of blood pressure and renal function..pdf (421.58 kB)

Urotensin-II System in Genetic Control of Blood Pressure and Renal Function

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posted on 2015-07-20, 09:19 authored by Radoslaw Debiec, Paraskevi Christofidou, Matthew Denniff, Lisa D. Bloomer, P. Bogdanski, L. Wojnar, K. Musialik, F. J. Charchar, John R. Thompson, D. Waterworth, K. Song, P. Vollenweider, G. Waeber, E. Zukowska-Szczechowska, Nilesh J. Samani, David Lambert, Maciej Tomaszewski
Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates.



PLoS One, 2013, 8 (12), e83137

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/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences


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